{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T07:04:41Z","timestamp":1772175881861,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1008948","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T00:00:00Z","timestamp":1609200000000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004435","name":"Association for International Cancer Research","doi-asserted-by":"publisher","award":["AICR 10-0908"],"award-info":[{"award-number":["AICR 10-0908"]}],"id":[{"id":"10.13039\/100004435","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107056\/Z\/15\/Z"],"award-info":[{"award-number":["107056\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"cancer research uk","doi-asserted-by":"crossref","award":["C6946\/A14492"],"award-info":[{"award-number":["C6946\/A14492"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["092096"],"award-info":[{"award-number":["092096"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HFSP","award":["LT000681\/2017-L"],"award-info":[{"award-number":["LT000681\/2017-L"]}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203767\/Z\/16\/Z"],"award-info":[{"award-number":["203767\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    During metazoan development, the cell cycle is remodelled to coordinate proliferation with differentiation. Developmental cues cause dramatic changes in the number and timing of replication initiation events, but the mechanisms and physiological importance of such changes are poorly understood. Cyclin-dependent kinases (CDKs) are important for regulating S-phase length in many metazoa, and here we show in the nematode\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    that an essential function of CDKs during early embryogenesis is to regulate the interactions between three replication initiation factors SLD-3, SLD-2 and MUS-101 (Dpb11\/TopBP1). Mutations that bypass the requirement for CDKs to generate interactions between these factors is partly sufficient for viability in the absence of Cyclin E, demonstrating that this is a critical embryonic function of this Cyclin. Both SLD-2 and SLD-3 are asymmetrically localised in the early embryo and the levels of these proteins inversely correlate with S-phase length. We also show that SLD-2 asymmetry is determined by direct interaction with the polarity protein PKC-3. This study explains an essential function of CDKs for replication initiation in a metazoan and provides the first direct molecular mechanism through which polarization of the embryo is coordinated with DNA replication initiation factors.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1008948","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T14:53:13Z","timestamp":1608043993000},"page":"e1008948","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of the critical replication targets of CDK reveals direct regulation of replication initiation factors by the embryo polarity machinery in C. elegans"],"prefix":"10.1371","volume":"16","author":[{"given":"Vincent","family":"Gaggioli","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1841-0273","authenticated-orcid":true,"given":"Manuela R.","family":"Kieninger","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6102-7141","authenticated-orcid":true,"given":"Anna","family":"Klucnika","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3885-1332","authenticated-orcid":true,"given":"Richard","family":"Butler","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5707-1083","authenticated-orcid":true,"given":"Philip","family":"Zegerman","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"issue":"3","key":"pgen.1008948.ref001","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1242\/dev.061838","article-title":"Regulation of DNA replication during development","volume":"139","author":"J Nordman","year":"2012","journal-title":"Development"},{"issue":"2","key":"pgen.1008948.ref002","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.yexcr.2015.07.022","article-title":"Cell cycle timing regulation during asynchronous divisions of the early C. elegans embryo","volume":"337","author":"N Tavernier","year":"2015","journal-title":"Experimental cell research"},{"issue":"4","key":"pgen.1008948.ref003","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/0092-8674(88)90575-2","article-title":"DNA synthesis and the control of embryonic gene expression in C. elegans","volume":"53","author":"LG Edgar","year":"1988","journal-title":"Cell"},{"issue":"5","key":"pgen.1008948.ref004","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1083\/jcb.200710018","article-title":"PAR proteins direct asymmetry of the cell cycle regulators Polo-like kinase and Cdc25","volume":"180","author":"DM Rivers","year":"2008","journal-title":"The Journal of cell biology"},{"issue":"7","key":"pgen.1008948.ref005","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1242\/dev.019075","article-title":"PLK-1 asymmetry contributes to asynchronous cell division of C. elegans embryos","volume":"135","author":"Y Budirahardja","year":"2008","journal-title":"Development"},{"issue":"17","key":"pgen.1008948.ref006","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1242\/dev.141226","article-title":"Cyclin CYB-3 controls both S-phase and mitosis and is asymmetrically distributed in the early C. elegans embryo","volume":"143","author":"WM Michael","year":"2016","journal-title":"Development"},{"issue":"12","key":"pgen.1008948.ref007","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1101\/gad.1933010","article-title":"How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?","volume":"24","author":"K. 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